An Approach to Chronic Diarrhoea 369

An Approach to Chronic Diarrhoea 369 An Approach to 62 Chronic Diarrhoea SHOBNA J BHATIA, PRAVEEN MATHEW Diarrhoea is a universal human experience. It is both osmotic forces generated by the transport of solutes, i.e. a symptom and a sign. electrolytes and nutrients. Molecular pathways of ion On symptoms it is defined as abnormal passage of and nutrient transport across the mucosa have been well three or more loose or liquid stools per day. As a sign, characterized. Identification of 5 specific congenital diarrhoea is an increase in stool weight (or volume) of diarrhoeal disorders (Table 1) has confirmed the more than 200 grams (or mL) per 24 hours on a Western importance of certain ion transporter mechanisms in diet. Previous studies have suggested that stool weight health and disease. is higher in Indians, and the upper limit of normal daily Table 1: Congenital diarrhoeal disorders stool weight for Indians is thus kept at 400 g. S. No Defective transport Mutated Diarrhoea should not be defined solely in terms of mechanism gene fecal weight because fecal consistency and weight correlate best with the ratio of water-holding capacity 1. Congenital chloride Chloride bicarbonate DRA diarrhoea exchange of insoluble solids to the total water present. 2. Glucose galactose Glucose stimulated SGLT – 1 Diarrhoea is generally considered acute when it lasts malabsorption sodium absorption less than two or three weeks. Chronic diarrhoea is 3. Congenital sodium Sodium hydrogen NHE 3 defined if symptoms persist for more than four weeks. diarrhoea exchange Chronic diarrhoea is a common clinical problem. 4. Congenital bile acid Sodium dependent ABAT Prevalence of chronic diarrhoea in the general popula- diarrhoea bile acid Absorption tion ranges between 3-5%. WHO has stated it could be 5. Congenital lactase Lactase phlorizin LCT between 5-20%. Unlike acute diarrhoea which is mostly deficiency hydrolase self-limited, chronic diarrhoea often persists, unless some therapy is instituted. This makes an accurate Congenital Diarrhoea Disorders diagnosis central to effective management. Effect of chronic diarrhoea on quality of life and health care Diarrhoea is often classified pathophysiologically as expenses are considerable. osmotic or secretory. Understanding Diarrhoea Osmotic diarrhoea is due to presence of poorly absorbed cations and anions (magnesium, sulfate, Diarrhoea is usually due to an excess of stool water phosphate), or poorly absorbed sugar or sugar alcohols rather than a decrease in water holding capacity of fecal (mannitol, sorbitol, lactulose) in bowel in excess, as these solids, implying an abnormality in water transport are poorly absorbed or transport mechanisms are within the gut. Diarrhoea results when there is a saturated at low intra-luminal ion concentration, leading reduction of water absorption by as little as 1% by small to water retention. Lactose intolerance, due to lactase or large bowel. Water itself is not actively transported deficiency, is the most common clinical syndrome which but moves across the intestinal mucosa secondary to results in osmotic diarrhoea. 370 Medicine Update Osmotic diarrhoea typically disappears with fasting by qualitative testing with Sudan stain or by quantitative or cessation of ingestion of the offending substance. Also analysis of a timed stool collection for fat. Inflammatory as electrolyte absorption is not impaired, the electrolyte diarrhoea typically contains blood or pus; these concentrations in stool water may be quite low. characteristics may be detected by a fecal blood test or, Secretory diarrhoea has many causes, it is either due staining for neutrophils in stool or lactoferrin, a to net secretion of chloride or bicarbonate, or inhibition neutrophil-derived protein. of net sodium absorption. The stimulus for secretion may come from the lumen (enterotoxins), the subepithelial Differential Diagnosis of Chronic Diarrhoea by Stool space or systemic circulation (vasoactive intestinal Characteristics peptide, calcitonin, histamine, inflammatory cytokines). I. Watery Diarrhoea Secretory diarrhoea may also result from absence of a specific absorptive pathway (congenital chlori- a. Osmotic diarrhoea—osmotic laxatives (Mg, diarrhoea), significant loss of surface area (extensive Phosphates, Sulfates) small bowel mucosal disease, as in celiac disease, Carbohydrate malabsorption inflammatory bowel disease, resective surgery etc), b. Secretory diarrhoea abnormal motility (diabetes mellitus, post-vagotomy diarrhoea) where the contact time between luminal Congenital syndromes (Congenital chloridarrhea) contents and epithelium is insufficient. Bacterial toxins Since there is a secreto/absorptive defect in secretory Bile acid malabsorption. diarrhoea, the stool electrolyte concentration is high and Inflammatory bowel disease (Crohn’s disease, the diarrhoea persists on fasting. microscopic colitis) The classification of diarrhoea as secretory or osmotic Drugs (most antibiotics, anti-neoplastic, antiarry- is helpful; pure secretory or pure osmotic diarrhoeas are thmics, theophylline) uncommon. Most clinically significant diarrhoeas are Laxative abuse complex, rather than being produced by a single pathophysiological mechanism. Disordered motility/regulation (postvagotomy, post-sympathetectomy, diabetic autonomic neuropathy, Recently a new variety of diarrhoea has been irritable bowel syndrome) described due to mutant neurogenin – 3, a transcriptor factor pivotal to development of pancreatic beta cell. Endocrine diarrhoea (hyperthyroidism, Addison’s Features of this disorder are that, diarrhoea ceases in disease, gastrinoma, VIPoma, pheochromocytoma). the fasting state, is induced when anything other than Other tumors (Colon cancer, lymphoma) water is ingested, mucosa of small intestine is normal, Idiopathic secretory diarrhoea. except for absence of enteroendocrine cell and there is no inflammatory component. The exact mechanism still II. Inflammatory Diarrhoea remains unclear. Inflammatory bowel disease (ulcerative colitis, Differential Diagnosis of Chronic Diarrhoea Crohn’s disease, ulcerative jejunocolitis) Clue to the site of diarrhoea can be obtained on the Infections (pseudomembranous colitis, invasive basis of volume of individual stools. When left side of bacterial infection like TB and Yersiniosis, ulcerating colon, including the rectosigmoid, is involved the stools viral infection like CMV and Herpes simplex, invasive are frequent, small in quantity, and may be painful. If parasitic infections like amebiasis) the source of diarrhoea is upstream in right colon or Ischemic colitis small bowel stools are large volume, and less frequent. Radiation colitis Another schema for classifying diarrhoea is based Neoplasia (colon cancer, lymphoma). on characteristic of stool produced—watery, fatty and inflammatory. III. Fatty Diarrhoea Watery stools are typically runny and lack pus, blood Malabsorption syndromes or fat. Watery diarrhoea is subdivided into secretory or osmotic depending on stool electrolyte concentration. Mucosal disease (Celiac disease, Whipple’s disease) Fatty stools have an excess of fat, which can be shown Short bowel syndrome An Approach to Chronic Diarrhoea 371 Small bowel bacterial overgrowth flatulence suggests increased fermentation of carbo- Mesenteric ischemia. hydrates by colonic bacteria, caused by ingestion of poorly absorbed carbohydrate or malabsorption of Maldigestion carbohydrate by small intestine. Pancreatic exocrine insufficiency Other coexisting symptoms such as abdominal pain, Inadequate luminal bile acid concentration. bloating, fever and weight loss should be enquired. There should be a thorough enquiry of drugs, previous Epidemiology of Chronic Diarrhoea in India surgery, radiation therapy, nutritional remedies, herbal Chronic diarrhoea is a common problem in India. medicines etc. Diet should be reviewed for ingestion of Most studies in India have classified the diarrhoea large quantities of poorly absorbable carbohydrates in depending on site of involvement—small bowel and fruit juices, soda pop, sugar-free candies, chewing gum large bowel diarrhoea. In studies from south India in etc. 1970s, tropical sprue was the commonest cause of History is essential to differentiate patients with chronic diarrhoea. It is now believed that frequency of functional bowel disorders, like irritable bowel TS is decreasing, possibly due to an improvement in syndrome (IBS) which may be suggested by abdominal standard of living, as also more frequent use of pain with defecation, long history usually dating to antibiotics. adolescence or young adulthood, excess mucus, exacer- In a recent study at a tertiary hospital in north India bations with stress etc. Factors against the diagnosis of on malabsorption, the causes were tropical sprue (39%), IBS are recent onset symptoms, older age group, Crohn’s disease (9%), celiac disease (9%), giardiasis (8%), nocturnal diarrhoea, weight loss, blood in stool and stool primary small intestinal bacterial overgrowth syndrome weight > 400 g/day. (6%), intestinal tuberculosis (4%), AIDS (2%), amyloi- dosis (2%), intestinal lymphangiectasiasis (1%), Examining the Patient panhypogammaglobulinemia (2%). Under representa- Physical examination may provide more direct tion of tuberculosis in the study was possibly because evidence of cause of diarrhoea. Characteristic skin chan- empirical treatment with anti-tubercular medicines was ges may be seen in celiac sprue (dermatitis herpiti- a common practice among community physicians. formis), Addison’s

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